Quorum sensing (QS) is a process of bacterial cell-cell communication that allows populations of bacteria to act like multicellular organisms by carrying out tasks in synchrony. The process involves secreted signaling molecules called autoinducers that the bacteria produce and release. Specifically, autoinducers accumulate at high cell densities, and when the concentration reaches a critical level, their detection drives synchronous group-wide changes in gene expression.
QS controls collective behaviors including bioluminescence, sporulation, biofilm formation, and virulence factor production. Quorum sensing plays a vital role in the pathogenicity of many bacteria because the ability to act as a coordinated group is essential for bacteria to successfully infect host organisms. Modulation of either the production or the detection of autoinducer molecules can abolish bacterial communication and render bacteria non-pathogenic.
The primary QS autoinducer in V. cholerae is known as CAI-1, which is the small molecule (S)-3-hydroxytridecan-4-one. CqsA synthase produces CAI-1 and CqsS is a membrane-spanning receptor that detects CAI-1. V. cholerae use a CqsA/CqsS quorum sensing circuit to control the production of virulence factors and require repression of this quorum sensing system to establish an infection in its host.
Typically in pathogenic bacteria that cause persistent infection, the accumulation of autoinducers at high cell densities triggers QS-mediated virulence factor production and biofilm formation. By contrast, Vibrio cholerae, which causes the acute intestinal disease cholera, displays an unusual QS profile: at high population density, QS initiates a cascade that suppresses virulence factor production (PCT/US2013/026837).
The distinct QS behavior exhibited by V. cholerae is attributed to its life cycle. Successful infection by V. cholerae leads to profuse diarrhea, which washes huge numbers of bacteria from the human intestine into the environment. Thus, at low cell density, the expression of genes for virulence and biofilm formation promotes establishment of infection in the host, while at high cell density, autoinducer-dependent repression of these traits promotes dissemination.
Several other clinically relevant bacteria are known to use a CqsA/CqsS quorum sensing circuit (e.g., V. parahaemolyticus and V. vulnificus). A homologous quorum sensing circuit identified in certain bacteria uses homologs of CqsA and CqsS found in e.g., Legionella species and in Nitrococcus mobilis, Burkholderia xenovorans, and Polaromonas spp.